The health of living organisms is maintained through a self-regulatory process called homeostasis. Limited, short-term perturbations of homeostasis caused by routine hardships do not affect health. In contrast, persistent long-term perturbations of homeostasis, also called “chronic stress,” are often associated with health disorders. Conditions that cause stress are called “stressors.”
Stress is a systemic condition and can therefore be analyzed not only in cells that were originally impacted by a stressor, but can also be analyzed in remote cells, tissues and biofluids. This is because stress triggers the activation of adaptive stress responses via a network of stress response (SR) pathways whose function is the maintenance of homeostasis. This network is large and involves hundreds of pathways and molecules. Varied groups of the SR pathways are activated by different stressors, in different organisms, and in different sample types. However, a small subset of the SR pathways respond universally to stress. These “universal” SR pathways are reproducibly activated by most stressors in most organisms.
Stress affects people at all ages. In addition to humans, stress also affects all living organisms (e.g. animals, plants and microorganisms) as well as entire ecosystems consisting of multiple different organisms. Stress has been linked to the risk and severity of health disorders and diseases. Stress also has adverse effects on reproduction, on the aging process and on longevity.
Current laboratory tests for stress rely on the measurement of hormones such as glucocorticoids (e.g. cortisol) and catecholamines (e.g. norepinephrine) in blood and saliva. (Arch. Gen. Psychiatry, 61: 394-401 (2004); Blood Pressure, 13: 287-294 (2004); and International Journal of Hygiene and Environmental Health, 208: 227-230. (2005).) These hormones are not suitable targets for a general analysis of stress, because they are not relevant to many types of stressors. Moreover, these individual stress biomarkers alone cannot discriminate between stress and responses to short-term hardships, such as school exams or exercise. Furthermore, these hormone-based stress tests are not useful to analyze the molecular mechanism of stress because these two biomarkers are only related to two SR pathways; the limbic hypothalamic-pituitary-adrenal axis (glucorticoids) and the sympathetic nervous system (catecholamines.) These two pathways are not representative of the universal SR pathways associated with chronic stress brought on by a broad range of different stressors. Indeed, many types of stressors do not activate these pathways. For example, these pathways are not activated by toxic chemicals. Moreover, these two stress tests have very limited applications in veterinary care, wildlife conservation and ecology, because they are not suitable for most nonhuman species.
There is therefore a need for systems and methods that are useful to analyze persistent homeostatic perturbations (i.e. chronic stress) caused by diverse types of stressors in many different types of organisms. There is also a need for methods that are useful to analyze the molecular mechanism of chronic stress in order to guide the development of new tools for diagnostics, prevention and treatment of stress.